What is a Category C pregnancy safety rating? A Guide for Understanding Medication Risks

October 12, 2025 •

3 min read

In 2015, the U.S. Food and Drug Administration (FDA) replaced its letter-based pregnancy safety categories, yet many still question what is a Category C pregnancy safety rating. This former classification indicated that while animal studies may have shown adverse effects, human data was lacking and the potential benefits of the drug could justify the risks.

Quick Summary

The former FDA Category C pregnancy rating indicated that animal studies showed a fetal risk, but there was insufficient human data. The potential benefits could outweigh the risks, requiring careful evaluation by a healthcare provider.

Key Points

Former FDA System: The Category C pregnancy safety rating was part of a now-defunct letter-based classification system (A, B, C, D, X) used by the FDA until 2015.
Meaning of Category C: This rating indicated that animal studies had shown adverse fetal effects, or that no human or animal data was available; therefore, risk could not be ruled out.
Risk vs. Benefit: For a Category C medication, the potential benefits to the pregnant patient were deemed significant enough to potentially outweigh the unknown or potential risks to the fetus.
Replaced by the PLLR: The FDA replaced the letter categories with the Pregnancy and Lactation Labeling Rule (PLLR), which uses detailed narrative summaries rather than simplistic letters.
Informed Decision-Making: Understanding the risk, whether from a former category or the new PLLR, requires a thorough discussion with a healthcare provider to weigh all factors.

The Former FDA Pregnancy Category System

For decades, the FDA utilized a five-tier, letter-based system (A, B, C, D, X) to classify the potential risk of medications during pregnancy. This system aimed to provide a quick reference for healthcare providers. While replaced, the old classification is still sometimes referenced, making it important to understand its definitions.

The previous pregnancy risk categories were defined as follows:

Category A: No risk shown in human studies in the first trimester, with no evidence of risk in later trimesters.
Category B: Animal studies show no risk, but human studies are lacking; or animal studies show risk, but human studies do not confirm it.
Category C: Animal studies show adverse effects on the fetus, and human studies are lacking. Use may be warranted if potential benefits outweigh risks.
Category D: Positive evidence of human fetal risk exists, but benefits in life-threatening situations may outweigh risks.
Category X: Evidence from animal or human studies shows fetal abnormalities or risk, and the risks outweigh any benefits. These drugs are contraindicated in pregnancy.

Understanding What is a Category C Pregnancy Safety Rating

Essentially, what is a Category C pregnancy safety rating meant that risk to the fetus could not be ruled out. This category was often used for newer drugs or those with insufficient human data. Since controlled drug trials on pregnant women are unethical, many medications fell into Category C if animal studies showed adverse effects or if data was completely absent.

A Category C rating did not definitively mean a drug was harmful but indicated uncertainty. The decision to use such a medication required a careful risk-benefit analysis with a healthcare provider, considering the mother's condition and alternative treatments.

The Shift to the Pregnancy and Lactation Labeling Rule (PLLR)

In 2015, the FDA replaced the letter categories with the Pregnancy and Lactation Labeling Rule (PLLR). The old system was criticized for being too simple and often misinterpreted. The PLLR provides more detailed, narrative information in three subsections:

Pregnancy (8.1): Summarizes risks, clinical considerations, and data.
Lactation (8.2): Details drug levels in breast milk and infant effects.
Females and Males of Reproductive Potential (8.3): Covers pregnancy testing, contraception, and infertility.

This new rule encourages more informed discussions between patients and providers.

Old vs. New: A Comparison of FDA Drug Labeling


Feature	Former FDA Pregnancy Categories	Pregnancy and Lactation Labeling Rule (PLLR)
Rating System	Simple letter categories (A, B, C, D, X).	Detailed narrative summaries of risk and benefit.
Data Sources	Minimal detail on the source of the risk data (e.g., animal vs. human).	Explicitly states the data sources (human, animal, pharmacologic).
Interpretation	Often misinterpreted as a simple letter grade (A = good, X = bad).	Requires careful reading and interpretation, but provides more context.
Decision Making	Led to general guidelines based on the category.	Facilitates individualized risk-benefit counseling based on comprehensive data.
Scope	Covered pregnancy, but not explicitly lactation or reproductive potential.	Expanded to include dedicated sections for Pregnancy, Lactation, and Reproductive Potential.
Update Mechanism	Outdated labels for many drugs, as the categories were fixed.	Requires continual updating of labels as new information becomes available.

Making Informed Decisions with Your Healthcare Provider

Discussing any medication use during pregnancy with a healthcare provider is essential. Your doctor will evaluate the severity of your condition, alternative treatments, your stage of pregnancy, and your individual health history. Both the old and new labeling systems aim to provide healthcare professionals with information to make safe and effective choices for both mother and baby.

Conclusion

The question of what is a Category C pregnancy safety rating refers to a past FDA classification indicating uncertain fetal risk, often due to limited human data. Although replaced by the more detailed Pregnancy and Lactation Labeling Rule (PLLR) in 2015, the concept underscores the complexity of assessing medication safety during pregnancy. The PLLR promotes clearer, evidence-based communication, enabling better discussions between healthcare providers and patients about treatment risks and benefits. Consulting with a healthcare provider remains crucial for making safe medication decisions during pregnancy. For more details on the current rules, refer to the FDA's official Pregnancy and Lactation Labeling resources.

Frequently Asked Questions

A Category C rating meant that potential risk to the fetus from the medication could not be ruled out, often because human data was insufficient and animal studies might have shown adverse effects.

No, the FDA replaced the letter-based pregnancy safety system, including Category C, in 2015 with the Pregnancy and Lactation Labeling Rule (PLLR).

The new system is the Pregnancy and Lactation Labeling Rule (PLLR). It uses detailed narrative summaries in three subsections: Pregnancy, Lactation, and Females and Males of Reproductive Potential.

The letter-based system was seen as overly simplistic and prone to misinterpretation. The PLLR provides more detailed, evidence-based information for better clinical decision-making.

Not necessarily. The rating indicated a lack of conclusive human safety data. The risk to the fetus was considered in the context of the potential benefit to the mother, especially for serious health conditions.

You should consult with your healthcare provider. The official drug labeling now includes a more comprehensive PLLR narrative. Your doctor can discuss the specific risks and benefits for your situation.

For prescription drugs approved before 2001, the old categories may still appear on some labels, but manufacturers were required to transition to the new PLLR system over time. All drugs approved after June 30, 2015, must use the new labeling.